Low Dose Insulin Works for DKA in Kids

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This study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

ORLANDO -- A half size insulin dose was as effective as a standard dose in resolving diabetic ketoacidosis in children, but offered a gentler fall in blood glucose, researchers reported here.

Resolution of diabetic ketoacidosis occurred faster on average -- but not significantly so -- among children with type 1 diabetes treated with 0.05 U/kg/hour of insulin versus 0.10 U/kg/hour (16.5 hours versus 17.2 hours, P=0.73), according to Karthi Nallasamy, MD, of the Postgraduate Institute of Medical Education and Research in Chandigarh, India, and colleagues.

Low dose insulin was also associated with a faster time for blood glucose to reach 250 mg/dL or less (6 hours versus 6.2), and was also associated with a significantly slower drop in blood sugar over the first hour of treatment (39.1 mg/dL versus 63.2 mg/dL, P=0.01), Nallasamy said at an oral presentation at the meeting of the American Academy of Pediatrics.

Nallasamy noted that current dosing recommendations for diabetic ketoacidosis "are not based on strong clinical evidence" and that lower doses could effectively resolve acidosis without risks of "possible association of rapid glucose fall and cerebral edema," as well as hypokalemia and hypoglycemia.

The authors conducted an open-label, randomized controlled trial of 50 children 12 and younger -- mean age 6.9 -- in diabetic ketoacidosis to compare the efficacy and safety of low-dose versus standard dose insulin.

The study endpoints were rate of fall in blood glucose until it reached 250 mg/dL or less, resolution of acidosis, incidence of cerebral edema, incidence of hypokalemia and hypoglycemia, and noninferiority.

At baseline, the children were screened for symptomatic cerebral edema, septic shock at presentation, anuria for more than 6 hours, and receipt of insulin before admission. They were then randomized to receive either a standard or low dose of insulin and monitored over the following hours to the study endpoints. Blood glucose was measured hourly, while blood gases and electrolytes were measured every 4 hours.

Low and standard dose groups were well matched for age, sex, admission weight, rate of malnutrition, new onset diabetic ketoacidosis, established diabetes, duration of diabetes, and previous incidence of diabetic ketoacidosis, as well as chemical characteristics, such as pH, blood glucose, sodium, corrected sodium, potassium, and phosphate.

After treatment, there was no difference in time for blood glucose to reach 250 mg/dL or less, absolute blood glucose fall until that parameter was reached, and hourly falls in blood glucose from hours 1 to 4, but it was noted that the first hour saw a significantly gentler fall in those treated with the lower dose of insulin.

Complications related to treatment were mostly no different between groups -- rates of hypoglycemia, treatment failure, and cerebral edema did not differ significantly.

There were significantly more children with hyperkalemia among those treated with the standard dose (12 versus 5, P=0.04), and seven of eight participants who were malnourished in the standard dose group developed hypokalemia compared with two of the seven in the low dose group (P=0.04).

Nallasamy noted that follow-up would involve a superiority trial with a larger sample size.

He noted that the study was limited by lack of measures of plasma insulin levels.

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